intro in pharmacology (10)

what is a drug?

a chemical substance which produces

eg could increase heart rate , pressure a specific physiological response within the body

what is a medicine

it is a preparation given for the treatment or prevention of disease

can be a drug or eexcipients: inactive ingredients

supports the drug, has an active ingredient in there which helps the drug perform well 

what types of medicines are the eyes related to 

diagnostic 

therapeutics: bacterial conjunctivitus , blood vessels dilate 

most px will be taking medications which could cause issues for the eye

how does a drug affect the body 

• pharmacodynamics 

• happening at a cellular level: the process is underpinned by drugs binding to proteins in or on cells. drugs influence the biochemical processes occuring in the cell 

• impact of tissues, organs → effects seen in organ systems 

• eg. topical anaesthetic eg lidocaine 

• eg targets nerve cells → stops sensation of pain, touch as cornea is very sensitive

• eg used to numb cornea in contact tonometry 

animal cells 

if drug finds it hard to enter the cell it acts on the protiens on the outside eg the glycolipids or glycoproteints of the cell membrane 

phopholipid bilayer: hydrophillic heads pointing out hydrophobic tail in layer 

drugs find it hard to cross the bilayer 

cell membrane

regulates what goes into or out the cell

phopholipid bilayer: phosphate heads are hydrophillic

lipid tails are hydrophobic: forms a stable layer in water free area between inner and outer layers of the membrane

proteins embedded, some act as carriers, some act as channels, some stick out the edge to form receptors

cholesterol for stability of structure

what is the cell membrane mainly made from

mianly made from lipid:

this influences which drugs can pass through

most drugs unable to pass through unaided

therefore effects exerted on membrane bound extracellular proteins

proteins 

chain of amino acids

20 different amino acids in human proteins 

determined by length of chain, order of amino acids, folding into the 3d shape 

20,000 diff proteins 

why do proteins make good drug targets

lots of different proteins means lots of potential targets

involved in many key physoological processes

certain proteins are only found in certain sites eg the heart has specific proteins so need drugs to target those exact proteins

what are the 4 main protein targets of drugs

the molecule of a drug must bind to a target to produce an effect

targets on/in a cell:

1. receptors

2. ion channels

3. carrier molecules

4. enzymes

drug target 1: receptors 

chemical messengers released allow communication and coordination between/within different cells tissues and organs:

common messengers are usuall:

• hormones

• neurotransmimtters like acetylcholine and noradrenaline which is important for pupil dilation

• mediators: histamine which is important for ocular allergies,like from allergic conjunctivitis

when allergic respinse occurs, histamine is released which makes bv more permeable causing them to leak  

whats a receptor

a site of tissue or molecule in a cell membrane that responds specifically to these messengers

the messengers bind to the receptor to initiate a response

may be referred to as a ligans which is used to describe a drug that binds to a receptor

ligand and receptors

ligans is the appropriate shape to fit into a receptor; eg lock and key

right shape = specificity : only that ligand will bind to particular receptor

binding cayses small change to the receptor site: triggers intracellular activity within the cell

when ligand binds to receptor activity is triggered

drugs and receptors

drug is mimicking the ligand and will bind to the receptor, preventing the ligand rom binding 

if the drug initiates a response and an activity is produced then this is known as an agonist . 2 drugs that work together 

if drug does not initiate a respinse/ prevents one then it is an antagonist drug. no activity is produced 

agonist 

bind to receptors and have the same effect as the ligand

it is a drug that replicates the action of a neurotransmitter 

what is a direct acting agonist

similar strucure to the transmtter and duplicates the action of the neurotransmitter by acting on receptor sites of the effector

what is an indirect acting agonist

cause the action to occur either by exciting the nerve fibre , thereby causing a release of the transmitter or by oreventing the recycling or reuptake of the transmitter, thus allowing it to continue its activity ]

phenylephrine 

mimics the neurotransmitter that stimulates the iris radial muscles 

causes pupil to get bigger

antagonists

either block the receptor sites or block the release of the neurotransitter thus preventing action of the effector

has affinity but no efficacy

tropicamide

it is an agononist

it blocks receptor sites on the iris sphincter muscle

temporarily paralyses the iris sphincter

pupil not able to constrict

sub types of receptors 

receptors belong to families; have classes and sub classes 

drugs can be targeted at specific sub types of receptors 

but they may accidently bind to other receptors of that class= unwanted side effects 

eg phenylephrine stimulates alpha-1 sub type in the iris 

drug target 2: ion channels

ion channels: atoms or molecules that carry a small charge

makes them more stable eg Na + are highly reactive in elemental uncharged state

= + cation , - anion

many processes rely on ions moving across cell membranes eg filteration of waste by kidneys, heart beats etc

channels regulate passage of ions across the cell membrane ]specific to their own ion eg potassium channels

can use a drug to block passage pf ions to prevent a response or make one occur

eg drug effects on ion channels

drug inserts itself into the channel, blocking the passage of ions

eg lidocaine

topical anaesthetics used by optometrists to numb the cornea

sodium ions cant move across so ap isnt generated, 

drug target 3: carrier molecules

proteins using ATP to actively transport substance across the cell membrane

could be transporting ions and neurotransmitters

eg fluoxetine block transporters for seratonin

drug target 4: enzymes

most biochemical reactions happening in each cell are catalysed by enyzmes

drugs generally inhibit enzymes : might be one step or might inhibit one step of a pathway

eg statins inhibit HMG CoA reductase : reduces cholesterol

ADME

how does a drug get to its site of action 

why are some medicines swalled, others injected , inhaled

why do some drugs last longer than others 

A: absorbs: how does it get into the body 

B: distributes: where does it go 

M: metabolites: how its broken down 

E: eliminates drugs: how does it leave 

oral dose of a drug: pharmacokinetic curve

at more blood reaches the plasma, the concentrtion of plama of drug rises and peaks

then drops

can work out amount of plasma needed for a max response

need the drug to reach certain threshold for it to work

when drops the pain eg might be returning here

at beginning the drug is disintegrating, absorpting and distrubuting itself to areas of the body, and by the time it drops, metabolism slows, extretion and storage occurs

drug administeration

progresses from initial dosage → biologically available form which can pass through or acorss tissues

3 pathways

1. topical : applied diectly to the site where the drug needs to act ey eye drops

2. enteral: absorbed into the bloodstream via digestive tract eg tablets

3. parentral: introduced directly into the body NOT via digestive system eg insulin injection, inhaler

enteral administeration

passes through the oesophagus , down into the stomach, then to the small intestine then to the large intestine 

the drug itself needs to be able to survive the harsh conditions of the stomach 

drug absorbed in the stomach and/or small intestine so it can reach the circulatory system 

once absorbed into the blood stream it will encounter the liver 

absorption in the stomach or small intesitne → liver → systemic circulation 

first pass metabolism

grugs are absorbed from the GI tract pass into the hepatic portal vein : travels directly to the liver

all of the substances that we absorb from the gut will first pass through the liver

steps of first pass metabolism

1. drug is absorbed by the gi tract

2. travels immediately to the liva via hepatic portal vein

3. metabolised by enzymes in the liver- can be to such extent that most of drug doesnt reach the systemic circulation

4. remaining drug is distribued around the body by circulatory system

drug distribution 

drugs distributed around the body via the bloodstream - very few drugs exert in the blood itself 

drugs need to move out of the bloodstream into the intersitual fluid to act on target proteins in/on cells 

drugs are not evenly distributed throughout the body 

many drugs do not travel dissolved in blood: bind to proteins in the blood 

only the free unbound drug that is available to have a therapeutic effect 

plasma protein binding

proteins in blood can help or hinder drug response

in the blood drug can be bound to proteins or unbound

bound drugs 

bound to plasma proteins eg albumin 

protein +drug = protein drug complex 

which reduces the amount of drug free to have a pharmacological effect 

drug plasma  protein forms a resevoir of drug , but only the free unbound drug is available to the tissues to exert a therapeutic effect 

helps drugs reach regions remote to administeration site 

hinders as when bound, cannot readily leave the capillaries and affect target tissues 

effect of drug solubility

• aqueous solubility:

water soluble drugs have difficulty crossing cell membranes, so will remain in circulation , stay in bloodstream and in danger of being excreted

they are cleared by the liver or kidneys so little practical use

• lipid solubility

enters the cell readilt therefore widespread distribution, easier to cross cell membranes so reach target

cell membrane as barriers to drug movement

polar molecules are hard to cross the cell membrane

cell membranes are mainly lipid, barrier to molecules excpet lipids , lipid soluble substances diffuse easily through the lipid bilayer

most drugs are lipid soluble in their unionised form whereas ionised forms are not

lidocaine swithces from ionised to unionised form : kept in acidid form to stay ionised, and unionsies when goes into the eye so it can pass through cell membrane

extent to which drug is ionised depends on local pH. kept in acidic standards

drugs that are polar or ionised are less anle to cross membranes which is why drugs often interact with proteins on the outside of the cells

drug metabolism

changing drugs via chemical reactions into compounds that are easier to eliminate

need to break down the drug into its metabolites

products of these chemical reactions= metabolites

as drugs are metabolised, their therapeutic effect diminshes , the drugs become less active ( but not always)

non polar drugs molecules are changed into polar molecules

usually metabolism decreases biological activity but may increase, retain or change

role of the liver in metabolism

blood being brought form hepatic portal vein reaching nutrients

moves through the sinusoids , and mix with enzymes and leave

main metabolic site= liver

perfused by blood containing frug from the gut

high conc of drug metabolising enzymes compared to other parts of the body

enzymes are key facilitators of durg metabolism:

aim of metabolism is to transform substances into a form that is easier for the kidneys to excrete 

• cytochrome P450

large family of enzymes 

• orally administered drugs will all pass through the liver and P450 metabolism 

extent of metabolism will determine the amount of drug that makes it into circulation and is available to target sites 

• diseases that affect the liver = reduced  ability to metabolise drug 

more will circulate in the body , so harder to break down  so will stay in the bloodstream  

drug metabolism: phase 1 reactions

modification

most common type: oxdation

aims to intoduce or expose functional groups: increase in polarity of compound

drug metabolism: phase 2 reaction

conjugation

attachment of an ionised group to the drug

makes drug more water soluble

what is a prodrug

most drugs become less active/useful once metabolised by prodrugs do not

a prodrug is pharamcologically inactive when administered, remain inactive until metabolised

converted into active metabolite once it is metabolised

why do we use prodrugs

active drug may be diffiuclt to administer

to enhance absorption - allows to use a low quantity of the drug so easier to pass barriers

protects from rapid metabolism

overcomes toxicity problems

could be used to increase ocular drug penetration or if active drug might vause issues outside the eye eg allergy

drug elimination 

• excretion: removing a drug and its metabolites from the body 

• major routes= via the kidneys and also bile/intestines 

• other routes: lungs, sweat, salica, tears, milk 

will be issues if patient has kidney issues as excretion is limited 

what 3 processes facilitate excretion in the kidney nephron

glomerular filteration

tubular secretion

tubule reabsorption

filteration at the glomerulus

hydrostattic pressure of blood flowing in capillaries drives glomerular filteration

pushes the blood acorss semi permeable membrane into bowmans capsule

allows molecules polar and non polar up to size of small proteins to move from blood into nephron

drugs which are protein bound will not cross the barrier

so small molecules can leave the blood to be exctreted

active secretion 

this is how majority od the drugs enter the tubule 

acitve as it is going against the concentration gradient : from cappilaries into the tubule 

there are 2 carrier systems: one for basic dugs one for acidic drugs 

if prolonged drug effect is required, agents can be administeed to block tubule secretion to slow excretion, and stay in bloodstream longer 

passive reabsorption

some of the drugs once in tubule will pass back into the blood stream from tubule

drugs enter the tubule, but could then be reabsorbed back into the blood

occurs via passive diffusion

majority of the water that has entered the nephron is reabsorbed back into the blood, and takes lipid soluble drugs with it. this increases time taken to eliminate lipid soluble drugs

drug specificity

usefulness of drug depends on its ability to act on a particular receptor

two way process: certain classes of drugs bind to certain receptors, or certain receptors recognise certain ligands

no drug has complete specifity - doesnt just stimulate just 1 receptor : other targets may be activiates, leading to side effects

affinity

the strength of attraction between a drug and its receptor - probability of a drug occupying a receptor at any given instant 

high affininty high probability 

high affininty on its own doesnt always produce a high response - eg antagonists may have a high affinity but produce no response 

lab measure= conc of a drug required to occupy 50% the available receptors 

eficacy

AKA intrinsic activity : measure of the ability of the drug to activate receptor and lead to a cellular response

measure of mgnitidue of the effect once drug is bound to receptor

max response achieved by a drug -

potency

the dose required to produce a specific intensity of response

highyl potent drug evokes a response at low concentrations

lower potency would need a higher concentration

ED50 can be a good indicator of potency ( effectice dose in 505 of population)

dose response curves 

graph which tracks the response to various conc or doses of a drug 

quantiative relationship between physiological responses and conc of agonist 

respons could be heart rate , blood pressuer etc 

will eventually hit a plateu: doses more than 400 will have on effect on response 

on log scale: raph stretched out so shows a conc can magnify the response with the dose

efficacy and potency demonstrated

comparing drug a and b

both drugs have equal efficiacy as both ahieve max response

have different potency

drug a is more potent than drug b as less conc is needed from a to achieve the same efficiacy than drug b

partial agonist

full agonist: max response prodyced by a drug = max response tissue can give

partial agonists: elicits a max respnse which falls short of thr max response tissue can give

has partial efficacy

therapeutic index 

measuring percentge of population that gets the response we want

low dose then 0% will be cured 

can also track toxi respinse/ bad side effects of the same drug 

higher dose, then greater proportion will experience a toxic response 

therapeutic index is the gap between the 2 curves

TD50= dose that gives a toxis response in 505 of population 

ED50= dose that is therapeutically effectice in 50 % of populatio 

safer drug= larger TI/larger gap 

large dose needed for a toxic response and small effective dose needed

 

competitive antagonists

competes with agonists for the binding site

without activation

increasing the agonist conc can overcome this as shifts our dose-response curve to the RIGHT

balance will be dtermined by relative affinity of each molecule for binding site

non competitive antagonist

does not compete with agonists for the binding site

agonist and antagonist can be bound to receptor simultanouesly

still opposes the action of the agonist

effect is to reduce the maximal effect produced

effect cant be reversed by increasing agonist conc

reversible competitive antagonist

will eventually dissociate from the receptor 

frees the receptor to be occupied again

eg tropicamide

cyclopentolate is reversable antagonist that temporarily inhibits the accom response

irreversible competitive antagonist

binds permanently to a receptor

strong bond to the receptor

permanently deactivates

body produces new set of receptors

plasma half life

the amount of time it takes for the conc of the drug in your plasma/drug to decrease by 50%

measures of how long a drug stays in the body

can indicate duration of action

drugs with a short half life need more frequent dosing

therapeutic range

may be that drug is only affective at a certain range/conc

need to ensure how long the patient will remain in therapeutic range for

drug interactions 

actions of a drug may be altered if taken with other substances 

eg 

other drugs 

foods

herbal product 

interactions might increase or decrease the effect of these drugs 

• pharmacodynamic interactions:

alters the sensitivity of tissues to another drug

agonistic or antagonistic effect 

occur at receptor level 

eg synergistic combination of using tropicamide and phenylephrine together to maximise pupil dilation 

pharmacokinetic interactions

can affect:

absorption

distribution, protein binding

metabolism

excretion

tend to affect the magnitude and duration of effect, rather than type of effect

practical advice:

when taking case history; make sure u ask/ record

all px current drus

other medicines other than counter that are being taken

herbal products

nutrional supplements

adverse drug reactions

a response to a medicinal product which is noxious and unintended (MHRA)

eg:

is px taking warfarin, likely to develop subconjunctival haemorrhages

amiodarone- can cause corneal lesions

biphosphates: swelling of the eye

part 2

what diognostix drugs do uk optometrists have acces to upon qualification

• pupil dilating: topicamide HCl and phenylephrine HCl

• accomodation relaxing: cyclopentolate HCl

• ocular suface and tear film investigation : fluorescein, lissamine green

• anaesthetics: proxymetacain HCl , tetracaine HCl, oxybuprocaine HCl , lidocaine HCl

what to ask the patient before installing drugs

have experienced adverse reactions to eye drops in the past

havs a history of drug induced adverse incidents

have any relevant medical conditions

take any systemic drugs

expected knoweledge of drugs

actions: how the drug works

interactions: any other drugs, herbal remedies, foods that might impact on the way the drug works

cautions: helps assess the risks, can be used, but cautiously

contraindications: more restrictive than a caution- drug should be avoided if this present

side effects: other side effects that this drug might cause

what should you explain to the patient

why are you instilling the drug

what effects the drops might have

how long they will last for

the side effects they might have

if dilating their pupils, that they might not be able to drive and must not undertake any activity which is not advsised after dilation and for how long

what to do if they experience an adverse reaction

leaflet for eye drops that are given to the patients

bnf

the british naitonal formulary

covers all the drugs available in the UK

emc: electronic version

eye specific drug: college of optometrist formulary

a px reportd in their case history that they are taing the antidepressant phenelzine 15mg every other day

wold u be able to use phenylephrine to dilate the px pupils?

on bnf:

drug → interactions → filter by drug name

storage of drugs in optometric practice

keep drugs out of reach of patients

store according to the manufacturers instructions

includes: out od reach and sight of children, out of light etc

room temp 8-25 degrees: eg tropicamide, cyclopentolate, lidocaine, phenylephrine, oxybuprocaine, tetracaine

fridge 2-8 degrees: proxymetacaine, chloramphenicol

packaging: minims

bausch and lomb

single use applicators containing aqueous solution : 0.5 mk approx 12 drops in one minim

preservative free

supplied in boxes of 20 applicators

sterilised by autoclavin at 115 degrees for 30 minutes

widely used in optom and opthalmology: must be fully conversant with this method of drug administeration

what to record

need to record the drug used including its dosage

the number of drops given

the time it was given

whether it was in the right eye or left or both

need the batch number

expiry date of the drug

procedure for obtaining the informed consent

1. inform px about the technique wish to use and the rationale

2. inform px that whether drops will sting , how long side effects nd chances of any adverse reactions

3. px informed not to drive after

4. if px has to operate hevay machinery or perform dangerous tasks, make ant=other appt for them where they can have their pupils dilated

safety checks

1. case history notes

2. does px hace any symptoms sugestive of angle closure

3. does px have any systemic or ocular diseases that could be aggravated by use of drug

4. does px have any systemic condition that could be aggravated by the instillation of drug

5. has px been given similar drops before and did they have a reaction to this

6. estimate size of anterior angle before instilling drugs

7. check for contraindications on slit lamp such as subluxated crystalline lens, disolcated intraocular lens implant, or pigmentary glaucoma, if any present then avoid mydriasis

choosing the approproate drug and dosage

does px have any systemic or ocular disease that could be aggravated by the drug . eg phenylephrine 105 shouldnt be given to those with severe cardiac diease, hypertension and hyoptension

does px have any disease that could influence choice of diagnostic drug. eg those with kidney disease must be given lowest dose of drug

eg iris colour: px with loghter iris respond uicker to drugs so lower doses given

drug instillation procedure

1. the px should be seated comfortably after washing hands and gaining consent

2. ask px to tilt their head backwards with the chin raised slightly

3. gently pull down their lower eyelid and pull it forward to form a pouch

4. insitl a drop into the temporal side of the pouch and gently release the lower eyelid

5. ask px to look don ad gentrl release upper eyelid over the eye

6. if 2 or more drops used, wait at least 3 mins between ech drop to ovoid the lacrimal pool from overfilling and falling out the eye after washing hands

7. dispose drug

occlusion of the nasolacrimal duct

can press finger over the lacrimal sac for 10 seconds

prevents excess drug entering nasolacrimal duct

disposal

• domestic waste: paper and cardboard, empty minim box, plastic/paper wrapper of the minim

• non hazardous healthcare waste: used contact tonometry probes. larger quantities of cls

• non hazardous pharmaceuticals waste : most pharmaceutical products: yellow bn with blue lid

• hazardous waste: blue bin, anything that has come intocontact with an infected eye, clinical: chloromphenicol . non clinical: cleaning products

• sharps: needles

how do i dispose of minims

• these are classes as no hazardous pharmaceutical waste

• whether used or unused

• dispose of in a medicine disposal box : normallu as a blue lid, incinerated

• this is for all pharmacy and prescirption only medicines that we use in minim form

exception = not pharmacologically , which can be disposed this way or emptied down the sink and place in a non hazardous healthcare waste

barriers for an eyedrop to cross

to reach its destination, drugs applied via eyedrops must cross anatomical barriers and bypass protective mechanisms of the eye

hits tear film → cornea

ony around 4% of the drug will reach the anterior chamber to go to the iris sphincter

conjunctival sac

lower fold created by conjunctiva over inside of the lids ( palpebral) and over the eyeball (bulbar)

max volume of fluid that can holf is approx 30 microlitres , if the lid is pulled down

have to leave time between each drop going into same eye otherwise 2nd drop washes out the first

most of the drug istilled here is cleared by the nasolacrimal drainage

route of our eyedrop

lower conjunctiva sac → (some spill onto eyelid or skin or around eye 0

mixes with tears →( some heads to puncta → nasolcrmal duct → systemic circulation or blown out of nose)

enters cornea → then into the aq hummour in the anterior chamber ( some might go to the trabecular meshwork or uveosclera and intothe systemic ciruclation)

then goes into the iris tissue

tear film

lipid layer on top which reduces evaporation of the tears

mucin layer sits against cornea, and helps spread the tears

volume approx 7-30 microlitres

tear turnover 16% per min : can increase to 80% per min following drop instillation

increased tear turnover is caused by drug irritation or ph deviation

blinking will also increase drainage due to eyelid muscle contraction

a large proportion of the drug is washed away within 2-3 minutes of drop instillation

cornea

has 3 layers: fat- water- fat

epithelium and endothelium: linked by cells with tight junctions, restrict passage of large molecules, relatively hydrophobic and lipophillic

stroma: plays a lesser role in resistance to drug passage

overall, corneal penetrance increases with hydrophobicity

corneal epithelium

high lipid content

non ionised lipid soluble molecules pass through easily

formidable barrier for water soluble molecules to pass

corneal stroma

water soluble molecyles pass easily across the stroma

ionised or polar moleucles can [ass across easily

non ionised molecules will have to ionise to assist movement

corneal endothelium

high lipid content

non ionised lipid soluble molecules find it easier to cross

forms of opthalmic drugs

aqueous solutions

oily solutions ( for drugs destoryed by water)

gels

ointments

creams

properties of opthalmic drugs : viscosity

• aq solution: low viscosity

short term retention in the eye

short term drug effect

higher risk of systemic absorption

better vision

• high viscosity: gel/ointments

long term retention in the eye

long term drug effect

lower risk of systemic absorption

poorer vision

influence of viscosity

• diagnostic drugs

lower viscosity aq solutions

short duration of contact with the eye

minimal ocular absorption of the drug

• therapeutic drugs (daytime use)

low viscosity

maintains good vision after drug instillation

repeated administeration of the drug required

• therapeutic drug ( night use ony)

high viscosity

maintains high contact time with the eye - good therapeutic effect

causes smeary vision, but this can be tolerated

properties of opthalmic drugs: pH

• pH of the tear fluid around 7.35 range 7-7.4

opthalmic drugs with pH significantly higher or lower than tear pH will sting

optimum comfort appears to be obtained with a slightly alkaline solution

pH of a solution can affect the efficiacy of a number of drugs

• buffers are used to control the pH of opthalmic preparations

acetic acis, boric acis, potassium bicarbonate, sodium citrate, sodium phosphate

• pH of solutions used in the eye normallu in the range 6-8

optometry eg of acids

anaesthtics we use usually sting on instillation due to their pH

there are weak bases: so to keep them stable they are formulated with a low pH. This keeps higher proportion ionised ( and stable)

properties of opthalmic drugs: tonicity

cornea is semi permeable membrane: tonicity of the pre corneal tear film can influence the fluid content of the cornea

tonicity of natural tears = 0.9% saline : range is 0.5% -2% tolerable

hyper vs hypotonic. eyedrops tend to be slghtly hypertonic

hypertonic can cause tearing and redness , tearing will reduce the conc of the drug

presevatives

• these are required for multi dose preparations

prevents contamination during storage and administeration

• preservatives can be toxic to human cells

normally used in low concs

• most commonly used eye drop preservative:

benzalkonium chloride

antimicrobial effect denatures proteins and disrupts cell membrane

has mild toxic effects on cornea and conjunctiva

has been shown to increase corneal permeability

what is mydriasis vs miosis

mydriasis= pupil dilation

miosis = pupil constriction

natural response of the pupil to bright light is miosis

why do we dilate a patients pupil

pupil is constantly changing shape

need to override this response to aid our examination

will allow a better view

when bright light is shon on the eye, the pupil will constrict making it hard to see past the pupil so drug overrides this and opens up the aperture